Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening. In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing. We collected blood, analysed cfDNA, and returned results to participants’ doctors. If a methylation signature indicative of cancer was detected, predicted cancer signal origin(s) informed diagnostic assessment. The primary outcome was time to, and extent of, diagnostic testing required to confirm the presence or absence of cancer. This trial is registered at , , and is completed. Between Dec 12, 2019, and Dec 4, 2020, we recruited 6662 participants. 4204 (63·5%) of 6621 participants with analysable results were women, 2417 (36·5%) were men, and 6071 (91·7%) were White. A cancer signal was detected in 92 (1·4%) of 6621 participants with analysable results. 35 (38%) participants were diagnosed with cancer (true positives) and 57 (62%) had no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began before MCED test results were reported, median time to diagnostic resolution was 79 days (IQR 37–219): 57 days (33–143) in true-positive and 162 days (44–248) in false-positive participants. Most participants had both laboratory tests (26 [79%] of 33 with true-positive results and 50 [88%] of 57 with false-positive results) and imaging (30 [91%] of 33 with true-positive results and 53 [93%] of 57 with false-positive results). Fewer procedures were done in participants with false-positive results (17 [30%] of 57) than true-positive results (27 [82%] of 33) and few had surgery (one with a false-positive result and three with a true-positive result). This study supports the feasibility of MCED screening for cancer and underscores the need for further research investigating the test's clinical utility. GRAIL.

中文翻译：

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多种癌症早期检测的血液检测 (PATHFINDER)：一项前瞻性队列研究

多癌早期检测 (MCED) 血液检测可以检测循环游离 DNA (cfDNA) 中的癌症信号。PATHFINDER 是一项前瞻性队列研究，调查 MCED 测试用于癌症筛查的可行性。在这项在美国七个健康网络的肿瘤科和初级保健门诊进行的前瞻性队列研究中，50 岁或以上、没有癌症体征或症状的成年人的方便样本同意接受 MCED 检测。我们采集了血液，分析了 cfDNA，并将结果返回给参与者的医生。如果检测到指示癌症的甲基化特征，则预测的癌症信号起源可为诊断评估提供信息。主要结果是确认癌症是否存在所需的诊断测试的时间和程度。该试验在 、 、 处注册并已完成。2019年12月12日至2020年12月4日期间，我们招募了6662名参与者。在 6621 名可分析结果的参与者中，4204 名 (63·5%) 为女性，2417 名 (36·5%) 为男性，6071 名 (91·7%) 为白人。在 6621 名参与者中，有 92 名 (1·4%) 检测到癌症信号，并具有可分析的结果。35 名 (38%) 参与者被诊断患有癌症（真阳性），57 名 (62%) 参与者未诊断出癌症（假阳性）。排除在报告 MCED 测试结果之前开始诊断评估的两名参与者，诊断解决的中位时间为 79 天 (IQR 37-219)：真阳性为 57 天 (33-143)，假阳性为 162 天 (44-248) - 积极的参与者。大多数参与者都进行了实验室检查（33 名参与者中的 26 名 [79%] 为真阳性结果，57 名参与者中的 50 名 [88%] 为假阳性结果）和影像学检查（33 名参与者中的 30 名 [91%] 为真阳性结果，53 名参与者为假阳性结果）。 [93%]（57 例中有假阳性结果）。假阳性结果的参与者（57 人中的 17 人 [30%]）进行的手术少于真阳性结果（33 人中的 27 人 [82%]），并且很少接受手术（1 人出现假阳性结果，3 人出现假阳性结果）。真阳性结果）。这项研究支持了 MCED 癌症筛查的可行性，并强调需要进一步研究该测试的临床实用性。圣杯。